Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

Short-term changes in Bruch's membrane opening-based morphometrics during the first week after trabeculectomy.

PURPOSE: To evaluate the dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head (ONH) using spectral-domain optical coherence tomography (SD-OCT) during the first week after glaucoma surgery by trabeculectomy with mitomycin C. METHODS: Prospective, longitudinal analysis of 25 eyes of 25 patients treated by trabeculectomy. Twenty-four eyes had evaluable postoperative SD-OCT examinations. Bruch's membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness were analyzed at baseline before surgery, 1 day, 2 to 3 days, and 1 week after surgery. Changes compared to baseline were correlated to intraocular pressure (IOP). RESULTS: One day after surgery, the mean BMO-MRW changed by + 26.17 µm, p = 0.001 (mean IOP reduction by 17.01 mmHg). This increase persisted on day 2-3 with a mean increase of BMO-MRW of + 25.33 µm, p = 0.001 (mean IOP reduction by 20.46 mmHg) and by week 1 with a mean BMO-MRW increase of + 33.17 µm, p < 0.001 (mean IOP reduction by 22.55 mmHg). The increase in BMO-MRW correlated significantly with the reduction of IOP on day 1 (Spearman's rho ρ = 0.656, p = 0.003) and d2-3 (Spearman's rho ρ = 0.479, p = 0.038). There was no statistically significant correlation found between the IOP and the increase in BMO-MRW in week 1. RNFL thickness showed no significant changes at day 1 as well as days 2-3 (p ≥ 0.078, respectively). It showed a small but significant increase in week 1 by 3.94 µm, p = 0.015. CONCLUSIONS: Structural reversal of disc cupping in BMO-MRW occurs as early as 1 day after trabeculectomy and correlates to the extent of the IOP reduction. During the whole first week after surgery, a strong increase in BMO-MRW can be noted. The changes in BMO-based parameters need to be considered when evaluating patients' longitudinal follow-up.

Ocular and Systemic Complement Activation during Anti-Vascular Endothelial Growth Factor Treatment and Age-Related Eye Disease Study 2 Dietary Supplementation in Neovascular Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to investigate the influence of dietary supplementation using Age-Related Eye Disease Study 2 (AREDS2) on complement activation in patients with neovascular age-related macular degeneration (nAMD) under ongoing treatment. METHODS: In this prospective, single-center, controlled, open-label investigator-initiated trial, eligible nAMD patients were randomized at a ratio of 1:1 in 2 groups: those with and without dietary AREDS2 supplementation for 4 weeks. Zinc, plasma, and aqueous humor (AH) complement levels were quantified via enzyme-linked immunosorbent assays. RESULTS: Fifty of 62 enrolled patients completed the trial (AREDS2 n = 27, controls n = 23). Systemic zinc and complement levels were not different at baseline between the 2 groups (p > 0.1). At the final visit, systemic zinc levels were significantly higher in the AREDS2 group (10.16 ± 2.08 µmol/L; 8.66 ± 1.17 µmol/L; p = 0.007), whereas systemic and AH complement levels were not different (p > 0.1). In both groups, no significant change was observed in systemic levels of C3, C3a, FH, FI, and sC5b-9 (p > 0.1). Only systemic complement component Ba showed an increase from baseline to the end visit (p = 0.01). This increase was higher in the control group (p = 0.02) than in the AREDS2 group (p = 0.23). CONCLUSIONS: Short-term dietary AREDS2 supplementation leads to a significant increase in systemic zinc levels without any influence on complement activation levels.

Dynamics of structural reversal in Bruch's membrane opening-based morphometrics after glaucoma drainage device surgery.

PURPOSE: Structural reversal of disc cupping is a known phenomenon after trabeculectomy. The aim of this retrospective, longitudinal, cross-sectional analysis was to evaluate the postoperative dynamics of Bruch's membrane opening-based morphometrics of the optic nerve head following glaucoma drainage device surgery. METHODS: Forty-three eyes, treated by glaucoma drainage device surgery, were included in the study. Individual changes in the spectral domain optic coherence tomography (SD-OCT) parameters Bruch's membrane opening minimum rim width (BMO-MRW), Bruch's membrane opening minimum rim area (BMO-MRA) and peripapillary retinal nerve fiber layer (RNFL) thickness as well as mean defect in 30-2 perimetry were analyzed. Changes were correlated to postoperative intraocular pressure levels over time. Available follow-up visits were aggregated and grouped into a short-term follow-up (20 to 180 days after surgery), a midterm follow-up (181 to 360 days after surgery) and a long-term follow-up (more than 360 days after surgery). RESULTS: In short-term follow-up, BMO-MRW and BMO-MRA increased significantly (p <= 0.034). This increase correlated negatively with the intraocular pressure at the time of the follow-up (Pearson's rho = - 0.49; p = 0.039). From 6 months after surgery on, there was no statistically significant change in BMO-MRW and BMO-MRA (p >= 0.207). RNFL thickness and mean defect of 30-2 perimetry showed no significant changes after GDD implantation (p >= 0.189). CONCLUSIONS: Lowering of intraocular pressure by glaucoma drainage device surgery leads to an increase of Bruch's membrane opening based parameters in the first 6 months after surgery. These changes have to be taken into account when evaluating patients' longitudinal follow-up after glaucoma drainage device implantation.

Impact of ab-interno trabeculectomy on Bruch's membrane opening-based morphometry of the optic nerve head for glaucoma progression analysis.

PURPOSE: To analyze the longitudinal change in Bruch's membrane opening minimal rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography (SD-OCT) after glaucoma surgery via ab-interno trabeculectomy in adult glaucoma patients. METHODS: Retrospective audit of 65 eyes of 65 participants undergoing ab-interno trabeculectomy using electroablation of the trabecular meshwork. In 53 eyes, surgery was combined with phacoemulsification and posterior chamber lens implantation. Pre- and postoperative SD-OCT examinations of the optic nerve head (ONH), intraocular pressure (IOP), and visual field data were analyzed. Longitudinal change in morphometric SD-OCT parameters of the ONH was compared and correlated to change in IOP and visual field function. RESULTS: BMO-MRW increased significantly between baseline (BL) and follow-up (FU) within the first 6 months after surgery (BL = 167.85 ± 90 µm; FU = 175.59 ± 89 µm; p = 0.034). This increase correlated with postoperative lowering of IOP (rho = - 0.41; p = 0.016). Nine months after surgery (range, 7-12 months), there was no significant change in BMO-MRW (BL = 196.79 ± 79; FU = 196.47 ± 85 µm; p = 0.95), while in later follow-up, a decrease of BMO-MRW was found (BL = 175.18 ± 78; FU = 168.65 ± 72; p = 0.05). RNFL thickness was unchanged in early (p > 0.16) and significantly decreased in later follow-up (p = 0.009). Mean deviation (MD) of visual field function did not show a significant change before and after surgery. CONCLUSION: Electroablative ab-interno trabeculectomy leads to a significant transient mild increase in BMO-MRW. This increase was shown to correlate with IOP lowering. Significant loss of BMO-MRW in later follow-up may reflect insufficient IOP reduction by surgery. The parameters RNFL thickness and MD seem less impacted directly by surgery.

Structural Reversal of Disc Cupping After Trabeculectomy Alters Bruch Membrane Opening-Based Parameters to Assess Neuroretinal Rim.

OBJECTIVE: To assess the impact of trabeculectomy for glaucoma on morphometric neuroretinal parameters of the optic nerve head (ONH) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Retrospective, interventional case series. METHODS: Participants: Eighty-eight eyes of 88 patients who underwent trabeculectomy with mitomycin C in 2016. INTERVENTION: All patients underwent trabeculectomy in 1 eye (study eye) and had evaluable SD-OCT examinations of the ONH to measure neuroretinal tissue before and at least at 1 of the 3-, 6-, and 12-month follow-up time points after surgery. MAIN OUTCOME MEASURES: Longitudinal change in Bruch membrane opening minimum rim width (BMO-MRW), Bruch membrane opening minimum rim area (BMO-MRA), peripapillary retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), and mean deviation in perimetry. RESULTS: In study eyes, BMO-MRW significantly increased postsurgically comparing baseline and follow-up examinations at 3 months (P = .012), at 6 months (P = .007), and at 1 year (P = .010) after trabeculectomy. The increase in BMO-MRW 6 months after surgery correlated with IOP reduction (r = 0.48; P = .001). BMO-MRA showed an equal increase (P ≤ .034). RNFL thickness remained stable between baseline and follow-up at 3, 6, and 12 months and showed a moderate loss after 18 months (P = .021) of follow-up. CONCLUSIONS: Structural reversal of disc cupping after trabeculectomy markedly influences Bruch membrane opening-based parameters for up to more than 1 year. Improvement in morphometry seems to correlate with the reduction of IOP while visual field function appears not to be influenced. In longitudinal follow-up of glaucoma patients by SD-OCT, evaluation of BMO-based parameters necessitates to reflect bias caused by surgery.